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  1. Article ; Online: Caspase-8 Promotes the Development of Pulmonary Hypertension.

    Satoh, Kimio

    Arteriosclerosis, thrombosis, and vascular biology

    2022  Volume 42, Issue 6, Page(s) 689–690

    MeSH term(s) Caspase 3 ; Caspase 8/genetics ; Humans ; Hypertension, Pulmonary/genetics ; Pulmonary Artery
    Chemical Substances Caspase 3 (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-)
    Language English
    Publishing date 2022-04-28
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.122.317727
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Sirtuin-7 as a Novel Therapeutic Target in Vascular Smooth Muscle Cell Proliferation and Remodeling.

    Satoh, Kimio

    Circulation journal : official journal of the Japanese Circulation Society

    2021  Volume 85, Issue 12, Page(s) 2241–2242

    MeSH term(s) Cell Proliferation ; Humans ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Sirtuins ; Vascular Remodeling
    Chemical Substances Sirtuins (EC 3.5.1.-)
    Language English
    Publishing date 2021-03-23
    Publishing country Japan
    Document type Editorial ; Comment
    ZDB-ID 2068090-9
    ISSN 1347-4820 ; 1346-9843
    ISSN (online) 1347-4820
    ISSN 1346-9843
    DOI 10.1253/circj.CJ-21-0137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Drug discovery focused on novel pathogenic proteins for pulmonary arterial hypertension.

    Satoh, Kimio

    Journal of cardiology

    2021  Volume 78, Issue 1, Page(s) 1–11

    Abstract: Pulmonary arterial hypertension (PAH) is a fatal disease in which the wall thickening and narrowing of pulmonary microvessels progress due to complicated interactions among processes such as endothelial dysfunction, the proliferation of pulmonary artery ... ...

    Abstract Pulmonary arterial hypertension (PAH) is a fatal disease in which the wall thickening and narrowing of pulmonary microvessels progress due to complicated interactions among processes such as endothelial dysfunction, the proliferation of pulmonary artery smooth muscle cells (PASMCs) and adventitial fibrocytes, and inflammatory cell infiltration. Early diagnosis of patients with PAH is difficult and lung transplantation is the only last choice to save severely ill patients. However, the number of donors is limited. Many patients with PAH show rapid progression and a high degree of pulmonary arterial remodeling characterized by the abnormal proliferation of PASMCs, which makes treatment difficult even with multidrug therapy comprising pulmonary vasodilators. Thus, it is important to develop novel therapy targeting factors other than vasodilation, such as PASMC proliferation. In the development of PAH, inflammation and oxidative stress are deeply involved in its pathogenesis. Excessive proliferation and apoptosis resistance in PASMCs are key mechanisms underlying PAH. Based on those characteristics, we recently screened novel pathogenic proteins and have performed drug discovery targeting those proteins. To confirm the clinical significance of this, we used patient-derived blood samples to evaluate biomarker potential for diagnosis and prognosis. Moreover, we conducted high throughput screening and found several inhibitors of the pathogenic proteins. In this review, we introduce the recent progress on basic and clinical PAH research, focusing on the screening of pathogenic proteins and drug discovery.
    MeSH term(s) Cell Proliferation ; Cells, Cultured ; Drug Discovery ; Drug Therapy, Combination ; Humans ; Hypertension, Pulmonary/drug therapy ; Hypertension, Pulmonary/etiology ; Leprostatic Agents/pharmacology ; Leprostatic Agents/therapeutic use ; Muscle, Smooth, Vascular ; Pulmonary Arterial Hypertension ; Pulmonary Artery
    Chemical Substances Leprostatic Agents
    Language English
    Publishing date 2021-02-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 639364-0
    ISSN 1876-4738 ; 0386-2887 ; 0914-5087
    ISSN (online) 1876-4738
    ISSN 0386-2887 ; 0914-5087
    DOI 10.1016/j.jjcc.2021.01.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: AMPKα2 Regulates Hypoxia-Inducible Factor-1α Stability and Neutrophil Survival to Promote Vascular Repair After Ischemia.

    Satoh, Kimio

    Circulation research

    2017  Volume 120, Issue 1, Page(s) 8–10

    MeSH term(s) Apoptosis ; Humans ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit ; Ischemia ; Neutrophils ; Vascular Endothelial Growth Factor A
    Chemical Substances Hypoxia-Inducible Factor 1, alpha Subunit ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2017-01-05
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.116.310217
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Development of Novel Therapies for Cardiovascular Diseases by Clinical Application of Basic Research.

    Satoh, Kimio

    Circulation journal : official journal of the Japanese Circulation Society

    2017  Volume 81, Issue 11, Page(s) 1557–1563

    Abstract: Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, inflammatory cells, activated platelets, and cardiac fibroblasts in response to oxidative stress. Excessive and continuous activation of the RhoA/Rho-kinase system promotes the secretion ...

    Abstract Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells, inflammatory cells, activated platelets, and cardiac fibroblasts in response to oxidative stress. Excessive and continuous activation of the RhoA/Rho-kinase system promotes the secretion of CyPA, resulting in the development of multiple cardiovascular diseases. Basigin (Bsg), a transmembrane glycoprotein that activates matrix metalloproteinases, is an extracellular receptor for CyPA that promotes cell proliferation and inflammation. Thus, the CyPA/Bsg system is potentially a novel therapeutic target for cardiovascular diseases. Importantly, plasma CyPA levels are increased in patients with coronary artery disease, abdominal aortic aneurysms, pulmonary hypertension, and heart failure. Moreover, plasma CyPA levels can predict all-cause death in patients with coronary artery disease and pulmonary hypertension. Additionally, plasma soluble Bsg levels are increased and predict all-cause death in patients with heart failure, suggesting that CyPA and Bsg are novel biomarkers for cardiovascular diseases. To discover further novel molecules targeting the CyPA/Bsg system, high-throughput screening of compounds found molecules that ameliorate the development of cardiovascular diseases. In addition to CyPA and Bsg, novel therapeutic targets and their inhibitors for patients with pulmonary arterial hypertension have been recently screened and identified. Ultimately, the final goal is to develop novel biomarkers and medications that will be useful for improving the prognosis and quality of life in patients with cardiovascular diseases.
    MeSH term(s) Basigin/antagonists & inhibitors ; Basigin/physiology ; Biomarkers/analysis ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/drug therapy ; Cyclophilin A/antagonists & inhibitors ; Cyclophilin A/secretion ; Humans ; Hypertension, Pulmonary/diagnosis ; Hypertension, Pulmonary/drug therapy ; Molecular Targeted Therapy/methods ; Molecular Targeted Therapy/trends ; Oxidative Stress ; Research/trends
    Chemical Substances BSG protein, human ; Biomarkers ; Basigin (136894-56-9) ; Cyclophilin A (EC 5.2.1.-)
    Language English
    Publishing date 2017-10-25
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 2068090-9
    ISSN 1347-4820 ; 1346-9843
    ISSN (online) 1347-4820
    ISSN 1346-9843
    DOI 10.1253/circj.CJ-17-1029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cyclophilin A in cardiovascular homeostasis and diseases.

    Satoh, Kimio

    The Tohoku journal of experimental medicine

    2015  Volume 235, Issue 1, Page(s) 1–15

    Abstract: Vascular homeostasis is regulated by complex interactions between many vascular cell components, including endothelial cells, vascular smooth muscle cells (VSMCs), adventitial inflammatory cells, and autonomic nervous system. The balance between oxidant ... ...

    Abstract Vascular homeostasis is regulated by complex interactions between many vascular cell components, including endothelial cells, vascular smooth muscle cells (VSMCs), adventitial inflammatory cells, and autonomic nervous system. The balance between oxidant and antioxidant systems determines intracellular redox status, and their imbalance can cause oxidative stress. Excessive oxidative stress is one of the important stimuli that induce cellular damage and dysregulation of vascular cell components, leading to vascular diseases through multiple pathways. Cyclophilin A (CyPA) is one of the causative proteins that mediate oxidative stress-induced cardiovascular dysfunction. CyPA was initially discovered as the intracellular receptor of the immunosuppressive drug cyclosporine 30 years ago. However, recent studies have established that CyPA is secreted from vascular cell components, such as endothelial cells and VSMCs. Extracellular CyPA augments the development of cardiovascular diseases. CyPA secretion is regulated by Rho-kinase, which contributes to the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. We recently reported that plasma CyPA levels are significantly higher in patients with coronary artery disease, which is associated with increased numbers of stenotic coronary arteries and the need for coronary intervention in such patients. Furthermore, we showed that the vascular erythropoietin (Epo)/Epo receptor system plays an important role in production of nitric oxide and maintenance of vascular redox state and homeostasis, with a potential mechanistic link to the Rho-kinase-CyPA pathway. In this article, I review the data on the protective role of the vascular Epo/Epo receptor system and discuss the roles of the CyPA/Rho-kinase system in cardiovascular diseases.
    MeSH term(s) Animals ; Cardiovascular Diseases/metabolism ; Cardiovascular System/metabolism ; Cardiovascular System/pathology ; Cyclophilin A/blood ; Cyclophilin A/metabolism ; Homeostasis ; Humans ; Oxidative Stress ; rho-Associated Kinases/metabolism
    Chemical Substances rho-Associated Kinases (EC 2.7.11.1) ; Cyclophilin A (EC 5.2.1.-)
    Language English
    Publishing date 2015
    Publishing country Japan
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 123477-8
    ISSN 1349-3329 ; 0040-8727
    ISSN (online) 1349-3329
    ISSN 0040-8727
    DOI 10.1620/tjem.235.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Globotriaosylceramide induces endothelial dysfunction in fabry disease.

    Satoh, Kimio

    Arteriosclerosis, thrombosis, and vascular biology

    2014  Volume 34, Issue 1, Page(s) 2–4

    MeSH term(s) Animals ; Endothelial Cells/enzymology ; Endothelium, Vascular/enzymology ; Fabry Disease/enzymology ; Humans ; Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism ; Lysosomes/metabolism ; Trihexosylceramides/metabolism
    Chemical Substances Intermediate-Conductance Calcium-Activated Potassium Channels ; Kcnn4 protein, mouse ; Trihexosylceramides ; globotriaosylceramide (71965-57-6)
    Language English
    Publishing date 2014-01
    Publishing country United States
    Document type Comment ; Editorial
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.113.302744
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Sirtuin 5 promotes ischemia/reperfusion-induced blood-brain barrier damage after stroke.

    Satoh, Kimio / Shimokawa, Hiroaki

    International journal of cardiology

    2018  Volume 284, Page(s) 77–78

    MeSH term(s) Blood-Brain Barrier ; Brain Ischemia ; Humans ; Reperfusion Injury ; Sirtuins ; Stroke
    Chemical Substances Sirtuins (EC 3.5.1.-)
    Language English
    Publishing date 2018-11-10
    Publishing country Netherlands
    Document type Editorial ; Comment
    ZDB-ID 779519-1
    ISSN 1874-1754 ; 0167-5273
    ISSN (online) 1874-1754
    ISSN 0167-5273
    DOI 10.1016/j.ijcard.2018.11.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Linoleic acid. A novel mechanism of endothelial cell dysfunction.

    Satoh, Kimio

    Circulation journal : official journal of the Japanese Circulation Society

    2013  Volume 77, Issue 11, Page(s) 2702–2703

    MeSH term(s) 3',5'-Cyclic-AMP Phosphodiesterases/biosynthesis ; Animals ; Calcium Signaling/drug effects ; Cyclic AMP/metabolism ; Endothelial Cells/metabolism ; Endothelium-Dependent Relaxing Factors/metabolism ; Linoleic Acid/pharmacology
    Chemical Substances Endothelium-Dependent Relaxing Factors ; Linoleic Acid (9KJL21T0QJ) ; Cyclic AMP (E0399OZS9N) ; 3',5'-Cyclic-AMP Phosphodiesterases (EC 3.1.4.17)
    Language English
    Publishing date 2013-09-27
    Publishing country Japan
    Document type Editorial ; Comment
    ZDB-ID 2068090-9
    ISSN 1347-4820 ; 1346-9843
    ISSN (online) 1347-4820
    ISSN 1346-9843
    DOI 10.1253/circj.cj-13-1155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: PIM1 (Provirus Integration Site For Moloney Murine Leukemia Virus) as a Novel Biomarker and Therapeutic Target in Pulmonary Arterial Hypertension: Another Evidence for Cancer Theory.

    Satoh, Kimio / Kikuchi, Nobuhiro / Shimokawa, Hiroaki

    Arteriosclerosis, thrombosis, and vascular biology

    2020  Volume 40, Issue 3, Page(s) 500–502

    MeSH term(s) Animals ; Biomarkers ; DNA Damage ; Leukemia ; Mice ; Moloney murine leukemia virus ; Neoplasms ; Pulmonary Arterial Hypertension ; Signal Transduction ; Virus Integration
    Chemical Substances Biomarkers
    Language English
    Publishing date 2020-02-26
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.120.313975
    Database MEDical Literature Analysis and Retrieval System OnLINE

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